Pseudotuberculosis (Yersinia pseudotuberculosis Infection)

Updated: Oct 11, 2017
  • Author: David R Haburchak, MD, FACP; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
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Overview

Practice Essentials

Yersinia pseudotuberculosis is a cold-tolerant bacterial species in the family Enterobacteriaceae that most commonly causes foodborne illness, typically enterocolitis or mesenteric lymphadenitis (pseudoappendicitis) in children. It can be associated with postinfectious complications such as erythema nodosum and reactive arthritis, and strains of Y pseudotuberculosis found in Asia appear to produce a superantigen-associated toxic erythema illness suggestive of scarlet fever.

Y pseudotuberculosis is common in wild animals and pork and may be transmitted by cross-contamination during food preparation.

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Background

First isolated in 1883, Y pseudotuberculosis is a gram-negative bacterium that belongs to the genus Yersinia in the Enterobacteriaceae family. Along with the more common Yersinia enterocolitica, it can cause gastrointestinal infection in various wild and domestic animals. Y pseudotuberculosis appears to be cold tolerant, allowing transmission via contaminated cold-stored foods, handling of infected animal tissues, and cross-contamination during food preparation.

Y pseudotuberculosis infection occurs worldwide but appears to be most common as sporadic disease in northern Europe and Asia, primarily as a zoonotic infection of rabbits and other mammals and birds. Y pseudotuberculosis infection has been attributed to domestic pork, cattle, sheep, deer, and rabbits, which can be asymptomatically infected, as well as pet dogs, birds, and reptiles. [1]

Many Y pseudotuberculosis outbreaks have occurred in zoos, animal-holding areas, and laboratory facilities.

Even adjusting for underreporting and difficulty in microbiological isolation, Y pseudotuberculosis appears to be a relatively rare pathogen in humans. Public health data are available from Russia, where it has been a reportable disease since 1988. [2] Children appear to be twelve times more likely to become infected than adults.

The most common clinical Y pseudotuberculosis syndromes are self-limited enterocolitis and mesenteric lymphadenitis (pseudoappendicitis), but septicemia may occur in immunocompromised hosts, resulting in metastatic infection. Common metastatic sites include the liver, spleen, lungs, and joints [3] or bone, particularly among individuals with cirrhosis, diabetes, and/or hemochromatosis. [4]

A special form of Y pseudotuberculosis infection called Far East scarlet–like fever (FESLF) has been described in association with specific strains [5] of Y pseudotuberculosis in Russia and Japan that demonstrate mitogen A, which acts as a superantigen. [2] In Japan, FESLF is known as Izumi fever.

Y pseudotuberculosis is associated with postinfectious complications such as erythema nodosum, reactive arthritis, iritis, and glomerulonephritis. Y pseudotuberculosis has also been implicated in the etiology of some cases of Kawasaki disease. [6]

Because of its 97% DNA homology with the agent that causes plague, Yersinia pestis, Y pseudotuberculosis is believed to have been the progenitor of the plague bacillus and is considered a model of bacterial evolution. [7] More optimistically, a specific strain of Y pseudotuberculosis, IP32953, has been modified into a potentially promising vaccine against bubonic and pneumonic plague. [8]

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Pathophysiology

Y pseudotuberculosis bears strong DNA, biochemical, and serological homology to the notorious agent of the Black Death, Y pestis, as well as a more common pathogen, Y enterocolitica. The pathogenic Yersinia species possess a wide range of chromosomal and plasmid-derived virulence factors, which allow entry, adherence, invasion, dissemination, and release from the host. [9] These include Type III Secretion system–encoded virulence plasmid pYV, the YPMa mitogen A superantigen, and the chromosomal high-pathogenicity island (HPI).

The HPI appears to be a complex of 5 genes involved in the production of an iron-siderophore yersiniabactin, which captures iron necessary and possibly rate-limiting for bacterial proliferation, [10] explaining the susceptibility among individuals with hemochromatosis or hemophilia. Other factors include YadA, responsible, but apparently not necessary, for invasion, as well as the surface protein MyfA, which promotes cellular attachment, and outer proteins (Yops), which inhibit host defense by inducing apoptosis, as well as a chromosomal regulon (PhoP/Q), which allows bacterial survival in macrophages.

Y pseudotuberculosis is primarily a zoonotic infection of variable severity. Human infection is relatively rare, and is a foodborne illness. It is usually acquired through the ingestion of contaminated water or food or possibly cross-contamination during preparation. Y pseudotuberculosis is apparently less resistant to desiccation than Y pestis, and therefore not soil borne. [1] It appears tolerant to cold, accounting for growth in cold-stored foodstuffs. The incubation period is believed to be 4-10 days after ingestion of a reasonably large dose of bacilli.

After entry and colonization of the gastrointestinal tract, Y pseudotuberculosis bacteria stealthily invade the intestinal mucosa and undergo "quiet" replication for 36-48 hours without a measurable host response owing to outer-protein inhibition of phagocytosis. [10] The infection then spreads to the Peyer patches and draining mesenteric lymph nodes. Y pseudotuberculosis disease typically manifests as an abscess-forming mesenteric lymphadenitis with fever and diarrhea, but can also lead to secondary perforation, intestinal obstruction, bleeding, intussusception, [11] and acute renal failure. [10]

Since the illness seems to target the terminal ileum, many cases are mistaken for appendicitis, hence the name of the organism.

Y pseudotuberculosis illness may be acute, subacute, or chronic but is usually self-limited. Bacteremia and sepsis, when it occurs, carries a high mortality rate.

In patients with underlying immunosuppressive disorders (uncontrolled diabetes mellitus, liver cirrhosis, or hemochromatosis or patients receiving immunosuppressive drugs), the bacteria may disseminate to the liver, spleen, and kidney, forming abscesses.

Postinfectious complications may include reactive arthritis, erythema nodosum, iritis, and glomerulonephritis.

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Epidemiology

Frequency

United States

The prevalence of Y pseudotuberculosis infection in the United States is unknown. It is likely underreported owing to lack of active surveillance and the need for special culture media for isolation.

International

While the distribution of Y pseudotuberculosis is worldwide, most Y pseudotuberculosis infections have been reported in countries of the northern hemisphere. Infection has been noted among domestic swine, rabbits, sheep, and deer in Italy, France, Australia, and New Zealand, [12, 2, 13, 14] with some serogroup specificity noted. Y pseudotuberculosis infection in Europe seems most prevalent in Germany, attributed to higher levels of pork consumption in that country. [10]

Animals are the major reservoir of Y pseudotuberculosis. This bacterium causes severe and, at times, lethal infections in susceptible animal species, in particular lagomorphs (hares and rabbits) during epizootics. In birds and rodents, Y pseudotuberculosis produces mild or asymptomatic infection.

Pseudotuberculosis may arise sporadically or in the form of outbreaks. Most cases are probably sporadic but likely misdiagnosed for viral enterocolitis, in part related to the labor-intensive laboratory testing for the pathogen in the stool of patients presenting with pseudotuberculosis.

Human Y pseudotuberculosis outbreaks after ingestion of contaminated milk products, undercooked or raw meat (eg, pork), fresh vegetables (carrots, lettuce), vegetable juices, and water have been reported in Canada, Finland, Russia, Japan, and New Zealand. [15] The scarlet fever–like syndrome has primarily been observed in Russia and Japan.

Most cases of pseudotuberculosis occur in winter and early spring, likely related to the enhanced growth characteristics of this pathogen in cold temperatures that occurs during long-term storage of vegetables during the winter. [10]

Mortality/Morbidity

Most Y pseudotuberculosis infections are self-limited with a low case-fatality rate. However, the uncommon septicemic form of illness that typically affects patients with underlying immunosuppressive disorders is associated with increased mortality rate (30%-40%).

Race

Y pseudotuberculosis infections appear to have no specific racial or ethnic predilection.

Sex

Y pseudotuberculosis infections are more common in men than in women. However, postinfectious complications (erythema nodosum and reactive arthritis) are more common in women.

Age

More than 75% of patients with Y pseudotuberculosis infection are aged 5-15 years.

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Prognosis

Most pseudotuberculosis cases are either minimally symptomatic or self-limited.

More severe forms of Y pseudotuberculosis infection, such as severe mesenteric lymphadenitis and those associated with metastatic infection, respond to antibiotic therapy, and death is very rare. However, in immunocompromised patients who develop Y pseudotuberculosis bloodstream infection, the reported case fatality rate is in the range of 30%-40%.

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Patient Education

People who prepare foods should be cautious about potential cross-contamination of foodstuffs, including baby formula, fresh vegetables, or other material stored cold, as Y pseudotuberculosis appears to be cold tolerant. It has been most commonly associated with pork products.

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